Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial)
Despite several treatment options and an initial high response rate to androgen deprivation therapy, the majority of prostate cancers will eventually become castration-resistant in the metastatic stage (mCRPC). Androgen receptor splice variant 7 (ARV7) is one of the best-characterized androgen recep...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-08-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/11/8/1099 |
| _version_ | 1797725430725214208 |
|---|---|
| author | Ivana Bratic Hench Richard Cathomas Luigi Costa Natalie Fischer Silke Gillessen Jürgen Hench Thomas Hermanns Eloïse Kremer Walter Mingrone Ricardo Pereira Mestre Heike Püschel Christian Rothermundt Christian Ruiz Markus Tolnay Philippe Von Burg Lukas Bubendorf Tatjana Vlajnic |
| author_facet | Ivana Bratic Hench Richard Cathomas Luigi Costa Natalie Fischer Silke Gillessen Jürgen Hench Thomas Hermanns Eloïse Kremer Walter Mingrone Ricardo Pereira Mestre Heike Püschel Christian Rothermundt Christian Ruiz Markus Tolnay Philippe Von Burg Lukas Bubendorf Tatjana Vlajnic |
| author_sort | Ivana Bratic Hench |
| collection | DOAJ |
| description | Despite several treatment options and an initial high response rate to androgen deprivation therapy, the majority of prostate cancers will eventually become castration-resistant in the metastatic stage (mCRPC). Androgen receptor splice variant 7 (ARV7) is one of the best-characterized androgen receptor (AR) variants whose expression in circulating tumor cells (CTCs) has been associated with enzalutamide resistance. ARV7 expression analysis before and during enzalutamide treatment could identify patients requiring alternative systemic therapies. However, a robust test for the assessment of the ARV7 status in patient samples is still missing. Here, we implemented an RT-qPCR-based assay for detection of AR full length (ARFL)/ARV7 expression in CTCs for clinical use. Additionally, as a proof-of-principle, we validated a cohort of 95 mCRPC patients initiating first line treatment with enzalutamide or enzalutamide/metformin within a clinical trial. A total of 95 mCRPC patients were analyzed at baseline of whom 27.3% (26/95) had ARFL+ARV7+, 23.1% (22/95) had ARFL+ARV7−, 23.1% (22/95) had ARFL−ARV7−, and 1.1% (1/95) had ARFL−ARV7+ CTCs. In 11.6% (11/95), no CTCs could be isolated. A total of 25/95 patients had another CTC analysis at progressive disease, of whom 48% (12/25) were ARV7+. Of those, 50% (6/12) were ARV7− and 50% (6/12) were ARV7+ at baseline. Our results show that mRNA analysis of isolated CTCs in mCRPC is feasible and allows for longitudinal endocrine agent response monitoring and hence could contribute to treatment optimization in mCRPC. |
| first_indexed | 2024-03-12T10:31:07Z |
| format | Article |
| id | doaj.art-cd1739821a594a61ab756dd2f03d8398 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T10:31:07Z |
| publishDate | 2019-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-cd1739821a594a61ab756dd2f03d83982023-09-02T09:14:36ZengMDPI AGCancers2072-66942019-08-01118109910.3390/cancers11081099cancers11081099Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial)Ivana Bratic Hench0Richard Cathomas1Luigi Costa2Natalie Fischer3Silke Gillessen4Jürgen Hench5Thomas Hermanns6Eloïse Kremer7Walter Mingrone8Ricardo Pereira Mestre9Heike Püschel10Christian Rothermundt11Christian Ruiz12Markus Tolnay13Philippe Von Burg14Lukas Bubendorf15Tatjana Vlajnic16Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, SwitzerlandDepartment of Oncology/Hematology, Cantonal Hospital Graubünden, 7000 Chur, SwitzerlandInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, SwitzerlandDepartment of Oncology, Cantonal Hospital Winterthur, 8401 Winterthur, SwitzerlandDepartment of Oncology/Hematology, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, SwitzerlandDepartment of Urology, University Hospital Zurich, University of Zurich, 8091 Zurich, SwitzerlandSwiss Group for Clinical Cancer Research (SAKK) Coordinating Center, 3008 Bern, SwitzerlandDepartment of Medical Oncology, Cantonal Hospital Olten, 4600 Olten, SwitzerlandClinic of Medical Oncology, Oncology Institute of Southern Switzerland, 6500 Bellinzona, SwitzerlandInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, SwitzerlandDepartment of Oncology/Hematology, Cantonal Hospital St. Gallen, 9007 St. Gallen, SwitzerlandInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, SwitzerlandInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, SwitzerlandDepartment of Oncology/Hematology, Hospital of Solothurn, 4500 Solothurn, SwitzerlandInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, SwitzerlandInstitute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, SwitzerlandDespite several treatment options and an initial high response rate to androgen deprivation therapy, the majority of prostate cancers will eventually become castration-resistant in the metastatic stage (mCRPC). Androgen receptor splice variant 7 (ARV7) is one of the best-characterized androgen receptor (AR) variants whose expression in circulating tumor cells (CTCs) has been associated with enzalutamide resistance. ARV7 expression analysis before and during enzalutamide treatment could identify patients requiring alternative systemic therapies. However, a robust test for the assessment of the ARV7 status in patient samples is still missing. Here, we implemented an RT-qPCR-based assay for detection of AR full length (ARFL)/ARV7 expression in CTCs for clinical use. Additionally, as a proof-of-principle, we validated a cohort of 95 mCRPC patients initiating first line treatment with enzalutamide or enzalutamide/metformin within a clinical trial. A total of 95 mCRPC patients were analyzed at baseline of whom 27.3% (26/95) had ARFL+ARV7+, 23.1% (22/95) had ARFL+ARV7−, 23.1% (22/95) had ARFL−ARV7−, and 1.1% (1/95) had ARFL−ARV7+ CTCs. In 11.6% (11/95), no CTCs could be isolated. A total of 25/95 patients had another CTC analysis at progressive disease, of whom 48% (12/25) were ARV7+. Of those, 50% (6/12) were ARV7− and 50% (6/12) were ARV7+ at baseline. Our results show that mRNA analysis of isolated CTCs in mCRPC is feasible and allows for longitudinal endocrine agent response monitoring and hence could contribute to treatment optimization in mCRPC.https://www.mdpi.com/2072-6694/11/8/1099mCRPCcirculating tumor cellsliquid biopsyandrogen receptorARV7 |
| spellingShingle | Ivana Bratic Hench Richard Cathomas Luigi Costa Natalie Fischer Silke Gillessen Jürgen Hench Thomas Hermanns Eloïse Kremer Walter Mingrone Ricardo Pereira Mestre Heike Püschel Christian Rothermundt Christian Ruiz Markus Tolnay Philippe Von Burg Lukas Bubendorf Tatjana Vlajnic Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial) Cancers mCRPC circulating tumor cells liquid biopsy androgen receptor ARV7 |
| title | Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial) |
| title_full | Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial) |
| title_fullStr | Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial) |
| title_full_unstemmed | Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial) |
| title_short | Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial) |
| title_sort | analysis of ar arv7 expression in isolated circulating tumor cells of patients with metastatic castration resistant prostate cancer sakk 08 14 improve trial |
| topic | mCRPC circulating tumor cells liquid biopsy androgen receptor ARV7 |
| url | https://www.mdpi.com/2072-6694/11/8/1099 |
| work_keys_str_mv | AT ivanabratichench analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT richardcathomas analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT luigicosta analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT nataliefischer analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT silkegillessen analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT jurgenhench analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT thomashermanns analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT eloisekremer analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT waltermingrone analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT ricardopereiramestre analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT heikepuschel analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT christianrothermundt analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT christianruiz analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT markustolnay analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT philippevonburg analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT lukasbubendorf analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial AT tatjanavlajnic analysisofararv7expressioninisolatedcirculatingtumorcellsofpatientswithmetastaticcastrationresistantprostatecancersakk0814improvetrial |